Occupational exposures are estimated to account for 9-15% of adult asthma cases. Among the most common causes of occupational asthma are isocyanates, reactive chemicals necessary to make polyurethane products (construction, automotive, military, medical, foam, coatings, adhesives). Millions of people are currently employed in industries that utilize isocyanates, and the work-force at risk for exposure continues to grow along with consumer demand for polyurethane. Recognition and diagnosis of isocyanate asthma can be challenging for both patients and physicians. Symptoms can be insidious and difficult to associate with the workplace, especially delayed responses, which are often mistakenly attributed to environmental triggers. In workers that develop immunologic hypersensitivity to isocyanate, long-lasting decrements in lung function may occur, and persist years after exposure ceases. Exposure is the only known risk factor for isocyanate asthma, and is the major target for disease prevention. Contemporary industrial hygiene technologies (respirators, "spray booths") reduce, but cannot eliminate workplace exposure. New cases of isocyanate asthma continue to occur in an estimated 5 - 10 % of those occupationally exposed, and represent a substantial public health problem. Despite the well-known allergenicity of isocyanates, occupational exposure assessment and disease screening is limited. Diagnostic assays that reliably differentiate sensitivity to isocyanate vs other asthma triggers are greatly needed for clinical practice as well as workplace screening. Biomarkers of isocyanate exposure are also needed to help guide and monitor industrial hygiene efforts. We hypothesize that isocyanate serology assays can be developed as a strategy for disease surveillance and industrial hygiene (exposure) monitoring to help protect individuals who are occupationally exposed to isocyanate. The serodiagnostics that would be developed in this project are new in two major ways. (1) They would be based upon novel "isocyanate antigens", produced using a mixed phase (vapor/aerosol/liquid) exposure system developed by our laboratory, which mimics the air/liquid interface of the bronchial fluid that lines human airways. (2) They would utilize biomarkers of allergy (IgE) to detect hypersensitive individuals, AND make use of immunologic markers of isocyanate exposure (IgG), to help target and monitor industrial hygiene efforts. The final product of this project would be a sensitive and specific ELISA kit, incorporating these unique qualities, which would have widespread value for clinicians, research scientists, industrial management and health care providers. Published findings from our laboratory predict the ELISA kit will be far superior to the only 1 other similar product currently available commercially (by a single supplier that dominates the market), and will dispel false conclusions that may have been drawn from previous studies using isocyanate antigens of questionable biologic relevance. PUBLIC HEALTH RELEVANCE: This grant application focuses on developing a better understanding the allergenicity of isocyanates, a major cause of occupational asthma world-wide. The expected product of the study will be a serodiagnostic assay, based upon novel isocyanate-protein complexes, that can be used to protect workers health by (1) identifying hypersensitive workers, (2) identifying exposure hot spots in the workplace (3) monitoring internal exposure and (4) monitoring the effectiveness of industrial hygiene efforts. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]